The characteristic clinical heterogeneity of
sickle cell anemia (HbSS) may be, in part, a result of its interactions with
alpha-thalassemia. Although
alpha-thalassemia clearly affects some hematologic features of HbSS, its role in modulating the vasoocclusive severity of disease is not clear. To further explore this relationship, we examined the incidence of painful episodes,
acute chest syndrome, aseptic
bone necrosis, and
leg ulcers in 3 patient groups with
sickle cell disease: (1) 2,147 patients over age 2 yr, stratified according to mean corpuscular volume (MCV); (2) 183 patients selected on the basis of microcytosis and elevated HbA2, on whom
globin biosynthesis studies were done; and (3) 125 patients who had
alpha-globin genotype assigned by
restriction endonuclease gene mapping. When patients were stratified by MCV, there was a reciprocal relationship between HbA2 levels and MCV, reflecting the presence of patients with beta o and
alpha-thalassemia in the low MCV groups. The erythrocyte indices and HbA2 levels in patients classified as HbSS-
alpha-thalassemia, by either
globin synthesis studies or gene mapping, were very similar to those previously reported by others. Neither microcytosis, beta o, or
alpha-thalassemia appeared to provide any clear protection from the vasoocclusive complication evaluated, and the prevalence of aseptic
necrosis was increased in patients with microcytosis over age 20 yr and in groups with
alpha-thalassemia. The effects of a reduced MCV and mean corpuscular hemoglobin concentration (MCHC), of possible benefit by themselves, when accompanied by a reduction in
hemolysis and rise in
hemoglobin concentration, as in HbSS-
alpha-thalassemia, may cause sufficient rise in blood viscosity in critical vascular beds to impair blood flow and negate any amelioration of vasoocclusive complications in HbSS.